A study is proposed of the biochemical mechanisms underlying the liver cell necrosis produced by hepatotoxins and by ischemia. Work on the former will concentrate on the mechanisms and consequences of disturbances in calcium homeostasis. In particular, the effect of the action of direct acting hepatotoxins (e.g. MMS) on the calcium permeability of cellular membranes will be studied. An attempt will be made to understand how covalent binding to these membranes effects their structure and function. Work on ischemic liver cell injury will concentrate on the mechanisms responsible for the accelerated degradation of membrane phospholipids previously described. In addition, the relationship between lipid depletion and membrane function will be explored.